Tasimelteon: first global approval

Drugs. 2014 Mar;74(4):505-11. doi: 10.1007/s40265-014-0200-1.


Tasimelteon (HETLIOZ™) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder. It is the first US FDA-approved medication for this orphan indication. Melatonin is thought to play a role in governing the body's natural sleep-wake cycle through physiological processes regulated in the suprachiasmatic nucleus of the hypothalamus. The hormone is secreted by the pineal gland, with onset typically occurring when daylight begins to dim. In healthy, sighted individuals, the endogenous circadian period is a little over 24 hours, but is entrained to the 24-hour day through exposure to environmental cues, such as light and darkness. In the absence of these cues, synchronisation is lost and the circadian rhythm follows the intrinsic non-24-hour clock, resulting in disorders like non-24-hour sleep-wake disorder. Because the rhythm of endogenous melatonin is considered to be a measure of the human circadian phase, the carefully timed administration of melatonin analogues, such as tasimelteon, can potentially promote circadian readjustment. This article summarizes the milestones in the development of tasimelteon leading to this first approval for the treatment of non-24-hour sleep-wake disorder.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Benzofurans / administration & dosage
  • Benzofurans / adverse effects
  • Benzofurans / pharmacokinetics
  • Benzofurans / therapeutic use*
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / adverse effects
  • Cyclopropanes / pharmacokinetics
  • Cyclopropanes / therapeutic use*
  • Drug Approval
  • Drug Chronotherapy
  • Humans
  • Patents as Topic
  • Receptor, Melatonin, MT1 / agonists*
  • Receptor, Melatonin, MT2 / agonists*
  • Sleep Disorders, Circadian Rhythm / drug therapy*
  • Sleep Disorders, Circadian Rhythm / metabolism
  • United States
  • United States Food and Drug Administration


  • Benzofurans
  • Cyclopropanes
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • tasimelteon